The aim of this project is to understand the physiological and ultrastructural basis of the blood-brain barrier, and to modify the permeability restriction of the barrier for use in central nervous system pharmacology. We have (a) elaborated the theory and provided morphological and physiological demonstration of osmotic opening of the barrier, (b) refined the technique of osmotic opening so that it can be accomplished without producing brain edema or apparent neurological damage, (c) used osmotic opening to increase barrier permeabiliy to intravascular measles antibody, the enzyme alpha-mannosidase, 125I-albumin and 3H-norepinephrine, (d) determined pressure threshold for barrier opening by acute carotid artery hypertension, (e) modified the permeability of the blood-aqueous and blood-vitreous barriers of the eye with hypertonic solutions. BIBLIOGRAPHIC REFERENCES: Spatz, M., Rap, Z.M., Rapoport, S.I., and Klatzo,I.: Effects of hypertonic solutions and of mercuric chloride on the uptake of (14C) glucose analogues by rabbit brain. Neuropathology Applied Neurobiology 2: 53-61, 1976. Laties, A.M. and Rapoport, S.I.: The blood-ocular barriers under osmotic stress: studies on the freeze-dried eye. Archives of Ophthalmology 94: 1086-1091, 1976.